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Biomedical subjects

D E Moulin

Publications and source records attributed to D E Moulin.

At least 19 recordsLinked to original sources
PubMed2005

Methadone in the management of intractable neuropathic noncancer pain.

OBJECTIVE: To evaluate the role of methadone in the management of intractable neuropathic noncancer pain. METHODS: A case series of 50 consecutive noncancer pain patients who were seen at a tertiary care centre and treated with oral methadone for a variety of intractable neuropathic pain states. RESULTS: The mean age was 52.7 years and the mean duration of follow-up was 13.9 months. Post-discectomy nerve root fibrosis, complex regional pain syndrome, peripheral neuropathy and central spinal cord pain syndromes were the most common diagnoses. Over 90% had been treated with one or more tricyclic antidepressants and anticonvulsants and a similar number had received other adjuvant analgesics. All patients had failed treatment with one or more conventional opioid analgesics (mean 2.8) at a mean maximal morphine dose of 384 mg (or equivalents) per day. Twelve patients had failed spinal cord stimulation. Nineteen patients (38%) did not tolerate initial methadone titration or thought their pain was worse on methadone. Five patients (10%) declared initial benefit but required repetitive dose escalation and eventually became non-responders. Twenty-six patients (52%) reported mild (4), moderate (15), marked (6) or complete (1) pain relief and continued on methadone at a mean maintenance dose of 159.8 mg/day for a mean duration of 21.3 months. Fourteen patients (28%) reported improved function on methadone relative to previous treatments. CONCLUSIONS: Methadone appears to have unique properties including N-methyl-D-aspartate antagonist activity that may make it especially useful in the management of intractable neuropathic pain. This observation needs to be tested in randomized, controlled trials.

Analgesics, Non-Narcotic↗
PubMed2001

Systemic drug treatment for chronic musculoskeletal pain.

OBJECTIVE: The purpose of this review was to determine how effective different classes of analgesic agents are in the management of chronic pain. METHODOLOGY: The literature search identified five systematic reviews and 18 randomized controlled trials to provide evidence about systemic drug treatment for chronic pain. RESULTS: Studies in the systematic reviews were mainly of low back pain, and studies in the randomized controlled trials were mainly of fibromyalgia. Other studies investigated of rheumatic pain, musculoskeletal pain, chronic low back pain, and temporomandibular pain. Classes of analgesic agents reviewed were antidepressants, nonsteroidal anti-inflammatory drugs, muscle relaxants, opioid analgesics, and a number of miscellaneous agents. CONCLUSIONS: For chronic pain, opioid analgesics provide benefit for up to 9 weeks (level 2). For chronic low back pain, the evidence shows that various types of nonsteroidal antiinflammatory drugs are equally effective or ineffective, and that antidepressants provide no benefit in the short to intermediate term (level 2). Muscle relaxants showed limited effectiveness (level 3) for chronic neck pain and for chronic low back pain for up to 4 weeks. For fibromyalgia, there is limited evidence (level 3) of the effectiveness of amitryptiline, ondansetron, zoldipem, or growth hormone, and evidence of no effectiveness for nonsteroidal anti-inflammatory drugs, malic acid with magnesium, calcitonin injections, or s-adenyl-L-methionine. For temporomandibular pain, oral sumatriptan is not effective (level 2). The remaining evidence was inadequate (level 4a) or contradictory (level 4b).

Analgesics, Opioid↗
PubMed2001

Treatment of neuropathic pain with venlafaxine.

OBJECTIVE: To report a case of successful treatment of neuropathic pain with venlafaxine. CASE REPORT: A 39-year-old white woman presented with neuropathic back pain. The patient obtained 50% pain relief with consecutive use of amitriptyline, desipramine, and imipramine. Anticholinergic effects prompted a switch to extended-release venlafaxine 75 mg/d. Pain relief was as effective with this therapy as with the tricyclic antidepressants. The absence of adverse effects allowed the patient to discontinue all laxatives. DISCUSSION: Venlafaxine is an antidepressant that inhibits reuptake of norepinephrine and serotonin. This is the major mechanism by which tricyclic antidepressants relieve neuropathic pain. Venlafaxine does not bind to muscarinic-cholinergic, histaminic or alpha1-adrenergic receptors responsible for the common adverse effects seen with tricyclic antidepressants. CONCLUSIONS: This report describes the efficacious use of venlafaxine in the treatment of neuropathic pain. Double-blind, randomized, controlled trials are needed to explore this further.

Adult↗
PubMed1998

Pain in central and peripheral demyelinating disorders.

Moderate to severe pain is a common feature of central and peripheral demyelinating disorders. Pain in multiple sclerosis tends to occur when the disease is well-established and usually lingers infinitely. Pain in Guillain-Barré syndrome tends to be particularly severe at the time of initial presentation and usually resolves over 8 to 12 weeks. Pain in both conditions is generally caused by either the direct effects of nerve injury or the result of paralysis and prolonged immobilization. Pain syndromes are well-defined in each disorder based on the underlying pathophysiology. Treatment involves a variety of pharmacologic and nonpharmacologic approaches individualized for each specific pain syndrome.

Analgesics↗
PubMed1998

A clinical evaluation of transdermal therapeutic system fentanyl for the treatment of cancer pain.

Fentanyl has been incorporated into a transdermal therapeutic system (TTS) containing a rate-limiting membrane that provides constant release of the opioid. TTS fentanyl provides continuous opioid delivery for up to 72 hr without the need for special equipment. After Institutional Review Board approval, 53 patients with cancer pain requiring 45 mg or more of oral morphine daily were admitted into an open-label, prospective, multicenter evaluation of TTS fentanyl for the relief of pain. After a 1-week stabilization on oral morphine, patients were transferred from morphine to an appropriate dose of TTS-fentanyl (25, 50, 75, or 100 micrograms/hr) administered as a transdermal patch every 3 days. TTS fentanyl was titrated to pain relief, and patients were followed up for as long as 3 months. Pain relief and the side effects of the medications were assessed daily. Twenty-six men and 27 women with a mean (+/- SD) age of 61 (+/- 12) years entered the study; 23 patients completed the full 84-day study. The mean duration of TTS fentanyl use was 58 +/- 32 days. The mean (+/- SEM) daily morphine dose during the last 2 days of stabilization was 189 (+/- 20) mg, and the mean initial fentanyl patch dose was 58 (+/- 6) micrograms/hr. The mean daily morphine dose taken "as needed" for breakthrough pain at study completion was 35 mg. The mean final fentanyl dosage at study completion was 169 (+/- 29) micrograms/hr. Pain relief was rated as good or excellent by 82% of patients during the treatment period. When asked to compare pain relief during the first month of TTS-fentanyl use to that provided by their last analgesic before study entry, 63% preferred TTS fentanyl. Side effects considered related to the fentanyl patch were nausea (13%), vomiting (8%), skin rash (8%), and drowsiness (4%). Thirty percent of patients reported adverse experiences related to the fentanyl patch, and 17% had to be discontinued from the study. We conclude that TTS fentanyl administered every 3 days for the treatment of cancer pain is effective, safe, and well tolerated by most patients.

Administration, Cutaneous↗
PubMed1998

Segmental hyperhidrosis as a manifestation of spinal and paraspinal disease.

BACKGROUND: Segmental hyperhidrosis is an uncommon finding which is usually associated with irritation or infiltration of pre-ganglionic sympathetic fibres or the sympathetic chain. METHODS: We report two cases of segmental hyperhidrosis with striking clinical features. RESULTS: In one case, a mesothelioma produced ipsilateral simultaneous underactivity and overactivity of sympathetic outflow and in the other case a thoracic central disc herniation was probably responsible for a band of sweating which clearly extended beyond the segmental level of injury. CONCLUSION: Segmental hyperhidrosis should trigger a search for structural disease in the spinal and paraspinal region.

Humans↗
PubMed1997

Pain in Guillain-Barré syndrome.

OBJECTIVES: To determine the character, intensity and frequency of pain in Guillain-Barré syndrome (GBS) and to evaluate the response to treatment. DESIGN: A prospective longitudinal study. SETTING: Academic hospital-based practices. PATIENTS: Fifty-five consecutive patients with GBS. INTERVENTIONS: Patients were evaluated on admission and at 2, 4, 8, 16, and 24 weeks. MAIN OUTCOME MEASURES: Character of pain, pain intensity using Visual Analogue Scale ([VAS] 0 to 10 cm) and Present Pain Intensity of McGill Pain Questionnaire, pain relief (VAS 0 to 10 cm), Disability Grading Scale for GBS. RESULTS: Forty-nine patients (89.1%) described pain during the course of their illness. On admission, mean pain intensity (VAS) was 4.7 +/- 3.3. However, 26 patients (47.3%) described pain that was either distressing, horrible, or excruciating (mean VAS, 7.0 +/- 2.0). The most common pain syndromes observed were deep aching back and leg pain and dysesthetic extremity pain. Pain intensity on admission correlated poorly with neurologic disability on admission (r = 0.26, p = 0.06) and throughout the period of study (r < 0.20, p > 0.10). Forty-one patients (74.5%) required opioid analgesics, with 16 (29.0%) receiving parenteral morphine to provide adequate pain relief. CONCLUSIONS: Moderate to severe pain is a common and early symptom of GBS and requires aggressive treatment. Pain intensity on admission is not a predictor of poor prognosis. Back and leg pain usually resolves over the first 8 weeks, but dysesthetic extremity pain may persist longer in 5 to 10% of patients despite motor recovery and the use of adjuvant analgesics.

Back↗
PubMed1996

Randomised trial of oral morphine for chronic non-cancer pain.

BACKGROUND: The use of opioid analgesics for chronic non-cancer pain is controversial. Some surveys report good pain relief and improvement in performance while others suggest a poor outcome with a propensity to psychological dependence or addiction. METHODS: We undertook a randomised double-blind crossover study to test the hypothesis that oral morphine relieves pain and improves the quality of life in patients with chronic regional pain of soft tissue or musculoskeletal origin who have not responded to codeine, anti-inflammatory agents, and antidepressants. Morphine was administered as a sustained-release preparation in doses up to 60 mg twice daily and compared with benztropine (active placebo) in doses up to 1 mg twice daily over three-week titration, six-week evaluation, and two-week washout phases. Pain intensity, pain relief, and drug liking were rated weekly and psychological features, functional status, and cognition were assessed at baseline and at the end of each evaluation phase. FINDINGS: After dose titration in the 46 patients who completed the study, the mean daily doses of drugs were morphine 83.5 mg and benztropine 1.7 mg. On visual analogue scales, the morphine group showed a reduction in pain intensity relative to placebo in period I (p = 0.01) and this group also fared better in a crossover analysis of the sum of pain intensity differences from baseline (p = 0.02). No other significant differences were detected. INTERPRETATION: In patients with treatment-resistant chronic regional pain of soft-tissue or musculoskeletal origin, nine weeks of oral morphine in doses up to 120 mg daily may confer analgesic benefit with a low risk of addiction but is unlikely to yield psychological or functional improvement.

Administration, Oral↗
PubMed1994

The dose-response relationship of controlled-release codeine (Codeine Contin) in chronic cancer pain.

The improved pain control provided by regular dosing of opioid analgesics in patients with severe cancer pain has been well established. However, the treatment of mild-to-moderate cancer pain is often limited to "as needed" dosing with fixed combinations of codeine or oxycodone plus a nonopioid analgesic, which do not allow optimal titration of the individual components. This randomized double-blind study was designed to evaluate the efficacy of controlled-release codeine (Codeine Contin) in patients with cancer pain, and to estimate its dose equivalence to a standard combination of acetaminophen plus codeine. Twenty-four patients with at least moderate cancer pain were randomized to Codeine Contin 100, 200, or 300 mg every 12 hr or acetaminophen plus codeine (600 mg/60 mg) every 6 hr. On days 1 and 4 of dosing, pain intensity and pain relief were assessed hourly for 12 hr. The sum of pain intensity differences (SPID) from baseline and the total pain relief (TOTPAR) scores demonstrated a dose-response relationship for Codeine Contin on days 1 and 4 that was statistically significant on day 1 and suggested greater analgesic efficacy on day 4, compared with day 1. Codeine Contin 150 mg every 12 hr was estimated to be equianalgesic to acetaminophen plus codeine (600 mg/60 mg) given every 6 hr. Because a similar equivalence was also demonstrated from analysis of adverse event data, it is concluded that Codeine Contin 150 mg produces analgesia and a side-effect profile similar to a 40% lower dose of codeine provided by the combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Simultaneous solid-phase extraction and chromatographic analysis of morphine and hydromorphone in plasma by high-performance liquid chromatography with electrochemical detection.

High-performance liquid chromatography has become an important analytical tool for the quantitation of opioid drugs. Using solid-phase extraction and coulometric electrochemical detection, we have developed a chromatographic method for the simultaneous measurement of morphine and hydromorphone which is both sensitive and specific. Using 1 ml of plasma, intra-assay and inter-assay data show that the detection limit for accurate quantitation of these compounds is about 1.2 ng/ml (coefficient of variation 11.6%) for morphine and 2.5 ng/ml (coefficient of variation 10.5%) for hydromorphone. The method is simple and readily adaptable to most pharmacokinetic studies and toxic screens involving these drugs.

Chromatography, High Pressure Liquid↗
PubMed1992

Subcutaneous narcotic infusions for cancer pain: treatment outcome and guidelines for use.

OBJECTIVE: To provide guidelines for the institution and maintenance of a continuous subcutaneous narcotic infusion program for cancer patients with chronic pain through an analysis of the narcotic requirements and treatment outcomes of patients who underwent such therapy and a comparison of the costs of two commonly used infusion systems. DESIGN: Retrospective study. SETTING: Tertiary care facilities and patients' homes. PATIENTS: Of 481 patients seen in consultation for cancer pain between July 1987 and April 1990, 60 (12%) met the eligibility criteria (i.e., standard medical management had failed, and they had adequate supervision at home). INTERVENTION: Continuous subcutaneous infusion with hydromorphone hydrochloride or morphine started on an inpatient basis and continued at home whenever possible. OUTCOME MEASURES: Patient selectivity, narcotic dosing requirements, discharge rate, patient preference for analgesic regimen, side effects, complications and cost-effectiveness. RESULTS: The mean initial maintenance infusion dose after dose titration was almost three times higher than the dose required before infusion (hydromorphone or equivalent 6.2 v. 2.1 mg/h). Eighteen patients died, and the remaining 42 were discharged home for a mean of 94.4 (standard deviation 128.3) days (extremes 12 and 741 days). The mean maximum infusion rate was 24.1 mg/h (extremes 0.5 and 180 mg/h). All but one of the patients preferred the infusion system to their previous oral analgesic regimen. Despite major dose escalations nausea and vomiting were well controlled in all cases. Twelve patients (20%) experienced serious systemic toxic effects or complications; six became encephalopathic, which necessitated dose reduction, five had a subcutaneous infection necessitating antibiotic treatment, and one had respiratory depression. The programmable computerized infusion pump was found to be more cost-effective than the disposable infusion device after a break-even point of 8 months. CONCLUSIONS: Continuous subcutaneous infusion of opioid drugs with the use of a portable programmable pump is safe and effective in selected patients who have failed to respond to standard medical treatment of their cancer pain. Dose titration may require rapid dose escalation, but this is usually well tolerated. For most communities embarking on such a program a programmable infusion system will be more cost-effective than a disposable system.

Costs and Cost Analysis↗
PubMed1991

Comparison of continuous subcutaneous and intravenous hydromorphone infusions for management of cancer pain.

To compare the safety and efficacy of subcutaneous and intravenous infusion of opioid analgesics, a randomised, double-blind, crossover trial was carried out in inpatients. 15 patients with severe cancer pain received two 48 h infusions of hydromorphone--one subcutaneously and one intravenously in randomly allocated order. The study was made double-blind by the use of two infusion pumps throughout; during the active subcutaneous infusion the intravenous pump delivered saline and vice versa. Serial measurements of pain intensity, pain relief, mood, and sedation by means of visual analogue scales showed no clinically or statistically significant difference between the two infusion routes. Side-effects were slight, and the mean number of morphine injections for breakthrough pain did not differ significantly between the routes (4.8 [SD 4.5] for intravenous vs 5.3 [5.6] for subcutaneous). Plasma hydromorphone concentrations measured at 24 h and 48 h of infusion showed stable steady-state pharmacokinetics; the mean bioavailability from subcutaneous infusion was 78% of that with intravenous infusion. Because of the simplicity, technical advantages, and cost-effectiveness of continuous subcutaneous opioid infusion into the chest wall or trunk, intravenous opioid infusion for the management of severe cancer pain should be abandoned.

Aged↗
PubMed1989

Pain in multiple sclerosis.

Pain is a common feature of well-established multiple sclerosis. Acute, subacute, and chronic pain syndromes have been defined. Chronic pain syndromes are usually associated with a myelopathy and are more common in women and in older individuals with a duration of disease greater than 5 years. The major chronic pain syndromes are dysesthetic extremity pain, back pain, and painful leg spasms. Treatment involves a variety of pharmacologic and nonpharmacologic approaches, but therapy must be individualized for each specific pain syndrome according to its own pathophysiology.

Adult↗
PubMed1988

Sublingual absorption of selected opioid analgesics.

Ongoing interest in the improvement of pain management with opioid analgesics had led to the investigation of sublingual opioid absorption. The present report determined the percent absorption of selected opioid analgesics from the oral cavity of normal subjects under conditions of controlled pH and swallowing when a 1.0 ml aliquot of the test drug was placed under the tongue for a 10-minute period. Compared with morphine sulfate at pH 6.5 (18% absorption), buprenorphine (55%), fentanyl (51%), and methadone (34%) were absorbed to a significantly greater extent (p less than 0.05), whereas levorphanol, hydromorphone, oxycodone, heroin, and the opioid antagonist naloxone were not. Overall, lipophilic drugs were better absorbed than were hydrophilic drugs. Plasma morphine concentration-time profiles indicate that the apparent sublingual bioavailability of morphine is only 9.0% +/- 11.9% (SD) of that after intramuscular administration. In the same subjects the estimated sublingual absorption was 22.4% +/- 9.2% (SD), indicating that the sublingual absorption method may overestimate apparent bioavailability. When the oral cavity was buffered to pH 8.5, methadone absorption was increased to 75%. Thus, an alkaline pH microenvironment that favors the unionized fraction of opioids increased sublingual drug absorption. Although absorption was found to be independent of drug concentration, it was contact time dependent for methadone and fentanyl but not for buprenorphine. These results indicate that although the sublingual absorption and apparent sublingual bioavailability of morphine are poor, the sublingual absorption of methadone, fentanyl, and buprenorphine under controlled conditions is relatively high.

Administration, Sublingual↗
PubMed1988

Pain syndromes in multiple sclerosis.

To determine the prevalence and nature of pain in multiple sclerosis, we evaluated by questionnaire, interview, and chart review 159 patients residing in Middlesex County and followed in the MS Clinic at University Hospital, London, Ontario, Canada. Eighty-eight patients (55%) had either an acute or chronic pain syndrome at some time during their disease. Fifteen patients (9%) with acute pain syndromes had episodes of paroxysmal tic-like pain diagnosed in seven as trigeminal neuralgia. Chronic pain syndromes, present for a mean duration of 4.9 years, occurred in 76 patients (48%) and included dysesthetic extremity pain (29%), back pain (14%), painful leg spasms (13%), and abdominal pain (2%). MS patients with pain were similar to the pain-free group in mean age of onset (34.0 versus 31.9 years), average duration of disease (13.3 versus 12.1 years), spinal cord involvement (97% for each group), and mean rating on Kurtzke Disability Status Scale (4.2 versus 3.5). They differed in sex ratio with a higher female-to-male ratio in the pain group (3:1 versus 1.4:1). Chronic pain is a common feature of well-established MS and is usually associated with a myelopathy. Therapy must be individualized for each specific pain syndrome.

Acute Disease↗
PubMed1986

Cerebrospinal fluid pharmacokinetics of intrathecal morphine sulfate and D-Ala2-D-Leu5-enkephalin.

Using an implantable pump system to deliver drugs and sample cerebrospinal fluid (CSF), we assessed rostral redistribution and systemic uptake after intrathecal bolus injection and steady-state infusion of morphine sulfate and the opioid peptide D-Ala2-D-Leu5-enkephalin (DADL) in two patients. Following bolus injection, the mean CSF elimination half-lives for morphine sulfate and DADL were 94 and 115 minutes, respectively. With the catheter tip at L2, the ratio of lumbar to cisternal (L/C) concentrations of morphine sulfate was about 7:1, and with the catheter tip at T10, the L/C ratios of morphine sulfate and DADL were approximately 2:1, indicating that this ratio is dependent in part on the level of intrathecal drug administration. CSF levels of morphine sulfate at steady state were three orders of magnitude higher than those in plasma. The CSF pharmacokinetics of morphine sulfate and DADL are similar, with supraspinal redistribution of these opioids via the CSF likely playing an important role in the generation of analgesia and central nervous system side effects.

Enkephalin, Leucine↗